DESCRIPTION: The adult cortex can reorganize in response to manipulations of the activity in inputs, to behavioral training and to other natural stimuli. These sorts of cortical reorganizations are associated with important phenomena, such as recovery of function after stroke and improvements in performance due to sensory training. Furthermore, deficits in the control of cortical plasticity may be related to neuropathies such as "phantom" pain and sensation after amputation to epilepsy to learning disabilities. Therefore, understanding the cellular mechanisms that underlie the plasticity of cortical assemblies can contribute both to the basic knowledge of neuronal processes, and to the understanding and treatment of neuropathies. Currently little is known about the cellular and synaptic events that underlie changes in cortical representations; changes in both excitation and inhibition, and sprouting of new connections have been hypothesized. In this proposal, experiments designed to examine possible synaptic and cellular mechanisms underlying cortical reorganizations in adult rat primary somatosensory cortex (Si) are detailed. The experiments make use of a novel in vivo/in vitro preparation, in which the location of the border between the lower jaw and forepaw representations in SI can be determined and visibly marked in vivo. EPSPs and IPSPs can be recorded in neurons close to the border in vitro. Previous work using this preparation has shown that anatomical and physiological properties of the local cortical circuitry, involving both excitation and inhibition, could underlie these representational borders. To further characterize properties of cortical circuitry with respect to normal and reorganized representational borders, several approaches are proposed: 1) Possible anatomical correlates of the observed physiological bias at the normal border will be determined by examining axonal projections of cortical neurons with respect to the border. Then, possible changes in both axonal and dendritic morphology will be examined with respect to representational borders reorganized by peripheral denervation of varying durations; 2) Physiological correlates of reorganization will also be assessed by examining changes in local excitation and inhibition in the cortex in the region of reorganization caused by peripheral denervation; 3) Characteristics of common forms of synaptic plasticity (long-term potentiation and long-term depression) will be examined, as changes in synaptic efficacy probably underlie some of the changes in excitation and inhibition previously observed after reorganization of the border. These data will provide specific evidence for possible roles for changes in excitation and inhibition during cortical reorganization, and possible anatomical and mechanistic correlates for the changes.